International Clinical Psychopharmacology最新文献

Medical Aid in Dying (MAiD) is the act of a healthcare provider ending a patient's life, at their request, due to unbearable suffering from a grievous and incurable disease. Access to MAiD has expanded in the last decade and, more recently, it has been made available for psychiatric illnesses in a few countries. Recent studies have found that such psychiatric requests are rapidly increasing and primarily involve mood disorders as the primary condition. Nevertheless, MAiD for psychiatric disorders is associated with significant controversy and debate, especially regarding the definition and determination of irremediability - that a given patient lacks any reasonable prospect for recovery. In this article, we report the case of a Canadian patient who was actively requesting Medical Assistance in Dying for severe and prolonged treatment-resistant depression until she experienced remarkable benefits from a course of intravenous ketamine infusions. To our knowledge, this is the first report of ketamine or any other intervention yielding remission in a patient who would have otherwise likely been eligible for MAiD for depression. We discuss implications for the evaluation of similar requests and, more specifically, why a trial of ketamine warrants consideration.

Mood disorders are recurrent/chronic diseases with variable clinical remission rates. Available antidepressants are not effective in all patients and often show a relevant response latency, with a range of adverse events, including weight gain and sexual dysfunction. Novel rapid agents were developed with the aim of overcoming at least in part these issues. Novel drugs target glutamate, gamma-aminobutyric acid, orexin, and other receptors, providing a broader range of pharmacodynamic mechanisms, that is, expected to increase the possibility of personalizing treatments on the individual clinical profile. These new drugs were developed with the aim of combining a rapid action, a tolerable profile, and higher effectiveness on specific symptoms, which were relatively poorly targeted by standard antidepressants, such as anhedonia and response to reward, suicidal ideation/behaviours, insomnia, cognitive deficits, and irritability. This review discusses the clinical specificity profile of new antidepressants, namely 4-chlorokynurenine (AV-101), dextromethorphan-bupropion, pregn-4-en-20-yn-3-one (PH-10), pimavanserin, PRAX-114, psilocybin, esmethadone (REL-1017/dextromethadone), seltorexant (JNJ-42847922/MIN-202), and zuranolone (SAGE-217). The main aim is to provide an overview of the efficacy/tolerability of these compounds in patients with mood disorders having different symptom/comorbidity patterns, to help clinicians in the optimization of the risk/benefit ratio when prescribing these drugs.

Antidepressant (AD)- emergent mood switch (AEMS) is a common complication of bipolar depression. This study aimed to investigate the prevalence and clinical correlates of subthreshold AEMS (i.e. not fulfilling DSM criteria for hypomanic episodes) in major depressive disorder (MDD) and, prognostically, its impact on AD treatment outcome and suicidality. The study involved 425 outpatients with MDD followed during the acute phase (12 weeks) and continuation (weeks 13-28) AD treatment. AEMS was assessed through the Altman Self-Rating Mania scale (ASRM ≥ 6). Several clinical features differentiated individuals with or without subthreshold AEMS (n = 204 vs. 221): negative self-perception [odds ratio (OR) 1.017-1.565]; panic disorder (OR 1.000-1.091); subthreshold hypomanic episodes (OR 1.466-13.352); childhood emotional abuse (OR 1.053-2.447); lifetime suicidal behaviour (OR 1.027-1.236); AD-related remission (χ 2  = 22.903 P  < 0.0001) and suicide ideation (χ 2  = 16.701 P  < 0.0001). In AEMS earlier onset showed a strong correlation with bipolar spectrum disorder (overall score: P  = 0.0053; mixed depression: P  = 0.0154; subthreshold hypomania: P  = 0.0150) whereas late-onset was associated with more severe suicidal behaviour ( P  < 0.001). In conclusion, our results demonstrate that subthreshold mood switches occur frequently in unipolar depression during acute AD treatment as well as in continuation phase. Time of switch onset seems to have the greatest diagnostic and prognostic value.

During the last decades the attempt to enlighten the pathobiological substrate of psychosis, from merely focusing on neurotransmitters, has expanded into new areas like the immune and redox systems. Indeed, the inflammatory hypothesis concerning psychosis etiopathology has exponentially grown with findings reflecting dysfunction/aberration of the immune/redox systems' effector components namely cytokines, chemokines, CRP, complement system, antibodies, pro-/anti-oxidants, oxidative stress byproducts just to name a few. Yet, we still lie far from comprehending the underlying cellular mechanisms, their causality directions, and the moderating/mediating parameters affecting these systems; let alone the inter-systemic (between immune and redox) interactions. Findings from preclinical studies on the stress field have provided evidence indicative of multifaceted interactions among the immune and redox components so tightly intertwined as a Gordian knot. Interestingly the literature concerning the interactions between these same systems in the context of psychosis appears minimal (if not absent) and ambiguous. This review attempts to draw a frame of the immune-redox systems' interactions starting from basic research on the stress field and expanding on clinical studies with cohorts with psychosis, hoping to instigate new avenues of research.

Schizophrenia is a chronic mental health condition treated with antipsychotics. A significant number of patients fail to respond to standard treatment and develop treatment-resistant schizophrenia (TRS). The only current treatment for TRS is clozapine, which has significant side effects and may only be effective in 40% of cases. We describe two cases of patients with TRS who have failed multiple antipsychotic trials and have had extensive hospitalization history due to aggression/hostility. Both patients responded to dual antipsychotic therapy with a long-acting injectable antipsychotic plus cariprazine. Both patients demonstrated improvement in hostility and cognition/memory. Cariprazine's novel mechanism of action may allow it to be uniquely effective in dual antipsychotic therapy for TRS. Cariprazine has a higher affinity than dopamine for D3 receptors and has a 10-fold higher affinity for D3 than D2. This may contribute to its pro-cognitive and anti-hostility effects. Further studies are warranted to determine the role of cariprazine in TRS.

Drug rash with eosinophilia and systemic symptoms (DRESS syndrome) is a rare systemic adverse drug reaction with a high mortality rate. Cases of DRESS syndrome have been reported with almost all classes of psychiatric medications, but data remains limited. We describe the case of a 33-year-old woman who presented with acute respiratory distress syndrome secondary to severe pulmonary blastomycosis. Her hospital course was complicated by severe agitation for which the psychiatry consult team was involved and several medications were trialed including quetiapine. She developed a diffuse erythematous rash during her hospital stay and later eosinophilia and transaminitis consistent with DRESS syndrome due to either quetiapine or lansoprazole based on the timeline. Both medications were discontinued, and she was started on a prednisone taper leading to resolution of the rash, eosinophilia, and transaminitis. Her HHV-6 IgG titer later returned elevated at 1:1280. DRESS syndrome along with many other cutaneous drug reactions can be associated with psychiatric medications and familiarity and recognition are imperative. There are limited reports of quetiapine-associated DRESS syndrome in the literature; however, rash and eosinophilia should alert psychiatrists to the potential for quetiapine to be a precipitant for DRESS syndrome.

Inflammatory processes in the brain play a role in acute mania etiopathogenesis. There is little evidence indicating the efficacy of celecoxib adjuvant therapy in treatmenting of manic episodes of bipolar disorder. Therefore, this clinical trial aimed to assess the celecoxib effect on treating acute mania. In a double-blind, placebo-controlled trial, 58 patients meeting the criteria for acute mania were enrolled. After considering eligibility, 45 patients were included in the study and randomly divided into two groups. The first group (23 patients) received sodium valproate 400 mg/day along with celecoxib 400 mg/day, and the second group (22 patients) received sodium valproate 400 mg/day and a placebo. The subjects were evaluated by the Young Mania Rating Scale (YMRS) at the beginning of the study and 9, 18, and 28 days following the initiation of the medication. Evaluation of baseline factors indicated a significant difference in age ( P  = 0.01) and psychiatric history ( P  = 0.02) between the two groups. However, other factors were similar between groups ( P  ≥ 0.05). Comparing the YMRS score between celecoxib and placebo groups revealed no significant difference on days 0, 9, 18, and 28. However, the YMRS score at the end of the study decreased by 16.05 ± 7.65 in the intervention group ( P  < 0.001) and 12.50 ± 5.98 in controls ( P  < 0.001) compared to the baseline, the trend of change was not significant between the two groups during the time of the study ( F  = 0.38; P  = 0.84). Although celecoxib adjuvant therapy indicated no considerable side effects, a longer treatment duration may be needed to detect its beneficial effects for treating acute mania in bipolar patients. Trial registration: Iran clinical trial register: IRCT20200306046708N1.

Restless leg syndrome (RLS) is a common but underestimated sensorimotor disorder that significantly affects the quality of life (QoL) which can be induced by antidepressants. This study aims to investigate the frequency and potential risk factors of RLS and side effects in selective serotonin reuptake inhibitors/serotonin and noradrenaline reuptake inhibitors (SSRI/SNRI) users. This cross-sectional study included 198 outpatients who received SSRI/SNRI for 4-8 weeks. Clinical evaluation was performed using the International Restless Leg Syndrome Study Group rating scale for RLS, Udvalg for Kliniske Undersøgelser side effects rating scale, and a short form 36 (SF-36) questionnaire for QoL. The frequency of RLS was 25%. RLS significantly increased with smoking and habituality. Also, habituality increased neurologic side effects reporting. The use of antipsychotics and calcium channel blockers decreased reporting of autonomic side effects. QoL decreased with RLS, psychiatric, neurologic, autonomic, and other side effects in different domains of SF-36. These findings suggested that SSRI/SNRI use could be associated with a higher risk of RLS, especially in smokers. QoL could be influenced negatively by RLS and all side effects. However, further prospective studies are needed to confirm these associations in large samples.

Lurasidone is an atypical antipsychotic approved for the treatment of schizophrenia and bipolar depression. It seems to have an antidepressant effect due to 5-HT7 as well as 5-HT2A and 5-HT1a receptor affinity. Here we present a case of a 19-year-old male patient with first-episode psychosis (FEP) and predominant depressive symptoms. Remarkable clinical and functional improvement was observed 3 months after the beginning of lurasidone treatment. The patient's depressive symptoms disappear with a dramatic reduction of psychotic ones, with good tolerance of the drug and without adverse effects. Lurasidone seems to be a promising treatment option for FEP with predominant depressive symptoms.